How can I lower my hemoglobin and hematocrit levels while on Testosterone Replacement Therapy (TRT)?

Managing Elevated Hemoglobin and Hematocrit on Testosterone Replacement Therapy

For patients with elevated hemoglobin and hematocrit while on TRT, therapeutic phlebotomy is the most effective intervention, along with potential dose reduction or switching to a transdermal formulation.

Understanding Erythrocytosis on TRT

Testosterone stimulates erythropoiesis, which commonly leads to increased hemoglobin and hematocrit levels in patients on TRT. This is one of the most frequent adverse effects of testosterone therapy 1:

• Injectable testosterone formulations are associated with higher risk (43.8% of patients) compared to transdermal preparations (15.4% of patients) 1
• Elevated hematocrit occurs in approximately 11% of patients (hematocrit >0.50 L/L) and 3.7% (hematocrit >0.52 L/L) 2
• Elevated hematocrit can increase blood viscosity, potentially increasing cardiovascular risk, especially in older patients or those with pre-existing vascular disease 1

Management Algorithm for Elevated Hemoglobin/Hematocrit on TRT

Step 1: Determine Severity and Intervention Threshold

• Monitor hematocrit regularly while on TRT
• According to AUA guidelines, intervention is warranted when hematocrit exceeds 54% 1

Step 2: Primary Interventions (in order of effectiveness)

1. Therapeutic phlebotomy

   • Most effective immediate intervention to reduce hematocrit 1
   • Can be performed through medical phlebotomy or blood donation
   • Note: Regular blood donation alone may be insufficient to maintain hematocrit below 54% in some patients 3

2. Modify TRT regimen

   • Reduce testosterone dose while maintaining therapeutic levels 1
   • Switch formulation from injectable to transdermal (gel or patch) 1, 2
   • Transdermal formulations cause less dramatic fluctuations in testosterone levels and lower rates of erythrocytosis

3. Temporarily discontinue testosterone in severe cases 1

   • Resume at lower dose or different formulation once hematocrit normalizes

Step 3: Address Modifiable Risk Factors

• Smoking cessation - tobacco use increases risk of erythrocytosis (OR 2.2) 2
• Weight management - higher BMI correlates with increased risk (OR 3.7) 2
• Evaluate for sleep apnea - can exacerbate erythrocytosis 1
• Assess for other medical conditions that may contribute to elevated hematocrit 2

Important Considerations and Precautions

Risk Factors for Developing Erythrocytosis on TRT

• Injectable testosterone formulations (especially undecanoate) 2
• Tobacco use 2
• Higher BMI 2
• Older age at initiation of TRT 2
• Pre-existing pulmonary conditions 2
• Concomitant SGLT2 inhibitor use in diabetic patients 4

Monitoring Recommendations

• Baseline hemoglobin/hematocrit before starting TRT 1
• Regular monitoring during treatment, especially in first year when largest increases occur 2
• Continue monitoring beyond first year as risk of developing erythrocytosis increases with exposure time (38% after 10 years) 2

Common Pitfalls to Avoid

1. Inadequate monitoring - hematocrit can increase even after years of stable therapy
2. Relying solely on blood donation - may be insufficient to control hematocrit 3
3. Ignoring modifiable risk factors - smoking and obesity significantly increase risk
4. Continuing same TRT regimen despite persistent elevations - formulation changes can make a significant difference

Special Considerations

For patients with concurrent type 2 diabetes on SGLT2 inhibitors, be particularly vigilant about monitoring hematocrit, as case reports indicate increased risk of erythrocytosis with this combination 4.

While hydroxyurea has been used to manage polycythemia in other conditions 5, it is not recommended for TRT-induced erythrocytosis due to potential serious adverse effects and availability of safer alternatives.